Genetic basis for clinical response to CTLA-4 blockade in melanoma.

ABSTRACT:

Background

Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells.

Methods

We obtained tumor tissue from patients with melanoma who were treated with ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors and matched blood samples. Somatic mutations and candidate neoantigens generated from these mutations were characterized. Neoantigen peptides were tested for the ability to activate lymphocytes from ipilimumab-treated patients.

Results

Maligna

SUBMITTER: Snyder A 

PROVIDER: S-EPMC4315319 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature